MK615 降低 RAGE 表达并抑制 TAGE 诱导的肝癌细胞增殖。
MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells.
机构信息
Second Department of Surgery, Dokkyo Medical University, School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
出版信息
World J Gastroenterol. 2010 Nov 14;16(42):5334-41. doi: 10.3748/wjg.v16.i42.5334.
AIM
To investigate the proliferative effect of advanced glycation end-products (AGEs) and the role of their cellular receptor (RAGE) on hepatocellular carcinoma (HCC) cells, and the inhibitory effects of MK615, an extract from Japanese apricot, against AGEs were also evaluated.
METHODS
Two HCC cell lines, HuH7 and HepG2, were used. Expression of RAGE was investigated by polymerase chain reaction, Western blotting, and flow cytometry (FACS). The effect of MK615 on RAGE expression was also evaluated by FACS. The proliferative effects of a control (unglycated bovine serum albumin), glucose-derived AGEs (Glc-AGE), and glyceraldehyde-derived AGEs (Glycer-AGE), and the anti-proliferative effect of MK615 against AGEs, were evaluated using MTT assays.
RESULTS
Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2. FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2. Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2. The growth indices for the control, Glc-AGE, and Glycer-AGE were 1.06 ± 0.08, 0.99 ± 0.04, and 1.38 ± 0.05, respectively, in HuH7 (P = 0.037), and were 1.03 ± 0.04, 1.04 ± 0.03, and 1.07 ± 0.05, respectively, in HepG2 (P > 0.05). When the cells were cultured simultaneously with Glycer-AGE and MK615, MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.
CONCLUSION
Only Glycer-AGE has a proliferative effect on HuH7, which expresses a higher level of RAGE. MK615 suppresses the proliferative effect of Glycer-AGE on HuH7 by decreasing the expression of RAGE.
目的
研究晚期糖基化终产物（AGEs）对肝癌细胞（HCC）的增殖作用及其细胞受体（RAGE）的作用，并评价日本甜杏仁提取物 MK615 对 AGEs 的抑制作用。
方法
使用两种 HCC 细胞系 HuH7 和 HepG2。通过聚合酶链反应、Western blot 和流式细胞术（FACS）检测 RAGE 的表达。还通过 FACS 评估 MK615 对 RAGE 表达的影响。用 MTT 法评价对照物（未糖基化牛血清白蛋白）、葡萄糖衍生的 AGEs（Glc-AGE）和甘油醛衍生的 AGEs（Glycer-AGE）的增殖作用以及 MK615 对 AGEs 的抗增殖作用。
结果
在 HuH7 和 HepG2 中均证实 RAGE 在 mRNA 和蛋白水平上的表达。FACS 显示 HuH7 中 RAGE 的表达水平高于 HepG2。用 0.1μg/mL 的 MK615 处理后，HuH7 中 RAGE 的表达水平从 24.3%降至 3.7%，HepG2 中从 6.2%降至 4.8%。对照物、Glc-AGE 和 Glycer-AGE 的生长指数分别为 HuH7 中的 1.06±0.08、0.99±0.04 和 1.38±0.05（P=0.037），HepG2 中的 1.03±0.04、1.04±0.03 和 1.07±0.05（P＞0.05）。当同时用 Glycer-AGE 和 MK615 培养细胞时，MK615 可阻断 Glycer-AGE 对 HuH7 的增殖作用。
结论
只有 Glycer-AGE 对表达更高水平 RAGE 的 HuH7 具有增殖作用。MK615 通过降低 RAGE 的表达来抑制 Glycer-AGE 对 HuH7 的增殖作用。
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